The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, effectively reduce coronary morbidity and mortality in high-risk adults. They are also some of the most widely prescribed medications in the United States. Their use in pediatrics, however, remains circumscribed. In this article we review the cholesterol hypothesis and focus on the knowledge base of the use of statins in adults and children. We pay particular attention to the known effects of statins in primary and secondary prevention of cardiovascular events. The toxicities of statins and their limitations in pediatrics are then considered. The use of statins in conjunction with noninvasive modalities of assessing atherosclerotic burden are also reviewed. Finally, we suggest methods to advance the use of statins in childhood that introduce their potential benefits to those individuals at highest risk for future events.

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Objectives After completing this article, readers should be able to:1. Describe the development of atherosclerotic plaque. 2. Discuss the two-pronged approach to addressing pediatric hypercholesterolemia advocated by the National Cholesterol Education Program and the American Academy of Pediatrics. 3. Describe the criteria for using lipid-lowering medication in children. 4. List risk factors for coronary artery disease that should be addressed in pediatric patients. IntroductionDespite significant declines in death rates from heart disease in recent years, this continues to be the leading cause of death in the United States. In 1999, heart disease was responsible for more than 30% of all deaths, with ischemic heart disease representing 65% of this total. With improved mortality rates of coronary artery disease (CAD) has come greater understanding of how atherosclerosis arises and may be prevented. This review summarizes recent findings regarding the development of cardiovascular disease and alerts pediatricians to how they can screen patients for precursors of CAD. It provides primary and secondary prevention strategies to manage risk factors when they are detected and directs readers to sources that include detailed guidelines for the risk factors that are discussed. Current Understanding of AtherosclerosisCentral to an appreciation of childhood risk factors for adult heart disease is an understanding of how the principal feature of coronary artery disease-the atherosclerotic plaque-develops. Rather than a simple accumulation of cholesterol on the intimal surface of vessel walls, the atherosclerotic plaque represents the culmination of a complex series of events involving inflammatory mediators, macrophages, and activated T lymphocytes in addition to circulating lipoproteins.The sequence begins when low-density lipoprotein (LDL) particles, those composites of lipid and protein designed to transport cholesterol from the liver and intestine to other organs, accumulate beneath the endothelial layer of the arterial wall. There, the central lipid portion of the LDL particle undergoes oxidation, and the proteins on the surface of the particle undergo glycation. These reactions stimulate endothelial and smooth muscle cells to elaborate chemical signals that attract and activate circulating monocytes and T lymphocytes. Activated monocytes and lymphocytes amplify the initial immune response, and in particular, as monocytes mature into macrophages, these cells express specific receptors that allow them to engulf the excess LDL. The resulting lipid-laden macrophages or foam cells combine with activated T cells to form a fatty streak, the initial atherosclerotic element, on the intimal surface of the coronary artery.As endothelial cells, macrophages, and T cells continue to secrete inflammatory mediators, smooth muscle cells from the intima are induced to migrate to the site to cover the luminal surface of the fatty streak. These cells secrete a collagen matrix that forms a fibrous cap or plaque that walls off the underlyin...